Impact of shift in testing guidelines for assessing HER2 status in breast cancer patients

"Many laboratories are documenting similar observations of an increase of HER2 equivocal cases since the 2013 updates," said Tafe. "We were one of the first laboratories in the country to report on it and our testing strategy is unique in that we perform primary HER2 fluorescence in-situ hybridization (FISH) testing where many labs utilize immunohistochemistry (IHC) as the primary test with reflex to FISH for equivocal cases."

Accurately determining HER2 status in patients with breast cancer is a critical prognostic and predictive factor and identifies patients who may benefit from treatment with anti-HER2 therapies. The 2013 ASCO/CAP revision of standards was the first since 2007. The updates lowered the threshold for HER2 and altered the equivocal category.

The Dartmouth group's retrospective review was based on comparison of one year's worth of cases prior to the guideline updates, and another year's worth of cases after the update. They found that the number of equivocal HER2 cases increased after the update, nearly half of which would have been negative by the 2007 guidelines. Additionally, a majority of the cases classified as equivocal with the 2007 guidelines would be reclassified as positive if using the 2013 criteria. This would have meant additional patients eligible for anti-HER2 therapy.

"We also found that HER2 immunohistochemistry was of limited utility in further classifying the FISH equivocal cases," explained Tafe. "Essentially, with the 2013 updates, cases that fall into the equivocal category are different than those previously considered equivocal. There is now a dilemma regarding how best to treat these patients and additional clinical studies are needed to answer this question."

In the same issue of the American Journal of Clinical Pathology is a report out of Oregon Health & Science University also evaluating the ASCO/CAP 2013 updates; similarly, they found an increase in the number of HER2 FISH equivocal results and positive cases. These two studies warranted an accompanying editorial highlighting their importance in illustrating the impact of these changes, what they may mean to patient care, and what questions remain unanswered.

Looking forward, from a laboratory perspective, Tafe and Marotti will evaluate whether alternative FISH probes are useful in further characterizing HER2 status in the equivocal cases. With external collaborators, the team will be evaluating interlaboratory reproducibility of equivocal results using different techniques. And importantly, the treatment and outcomes of patients with equivocal HER2 results will be followed to further assess the clinical impact of the revised guidelines.